We explore the recent undertaking in El Salvador to establish the country's first industry-higher education clusters in four economic sectors critical to growth and competitiveness: (1) information and communication technology; (2) light manufacturing; (3) energy and energy efficiency; and (4) agroindustry and food processing. These clusters take a systems approach to aligning higher education institutions (HEIs) with the talent and research needs of the private sector. Under the United States Agency for International Development's "Higher Education for Economic Growth" project, RTI International designed and facilitated a three-phase, 10-step process, beginning with the careful and transparent selection of sectors, followed by early engagement of key stakeholders, to form clusters and establish formal structures necessary for sustained multisector dialogue. The discourse ultimately culminated in the creation of data-driven strategic and operational plans guiding cluster actions. This paper documents this detailed process and highlights early successes and challenges observed. Finally, learnings and insights are also offered for those wishing to undertake a similar systems-level approach to collaboration between HEIs and industry with the goal of producing tangible, sector-level economic benefits.